The present invention relates to medicine and, more specifically, to a novel pharma-ceutical composition useful in the treatment of ophthalmic diseases.
At present, the role of free-radical peroxidation in the development of various diseases of the retina, optic nerve and other structures of the eye is well appreciated. For this reason, antioxidants are used increasingly in the treatment of ocular diseases. These compounds are able to alleviate inflammatory resorptive phenomena, to accelerate epithelization of the cornea and to reduce the incidence of dangerous complications that may result in the death of the eye.
The synthetic antioxidant Emoxipin (2-ethyl-6-methyl-4-oxypyridine) is known by its ability to reduce the capillary permeability and to inhibit blood coagulation. Injection of a 1% solution of this compound facilitates the resorption of intraocular hemorrhages. Emoxipin is clinically used in the treatment of chemical and thermal burns of the eye and in the keratoplasty of burn-related leukomas. However, monitoring of the blood coagulation system is required in the course of Emoxipin therapy, since this compound is liable to cause reccurrent hemorrhages (Egorov E. A., Shvedova A. A., Obraztsova I. S. Results of a clinical study of the antioxidant Emoxipin in the treatment of eye diseases. Vestnik Oftalmologii, 1989, No. 5, pp. 52-55, in Russian).
Also known in the prior art is the use of an 0.5% echinochrome solution in the treatment of eye burns (RU 2 038 088). Subconjunctival and parabulbar administration of an 0.5%-echinochrome solution to rabbits showed that it is able to facilitate epithelization of the cornea at early stages of the treatment of eye burns and to alleviate inflammatory processes in the eye.
However, clinical studies using an 0.5% echinochrome solution showed that patients experienced acute pain at the time of administration.
The objective of the present invention is to provide a novel and highly effective pharma-ceutical composition for the treatment of ophthalmic diseases, which would also meet the requirements that apply to injectable formulations.
The pharmaceutical composition of the present invention is based on echinochrome and has been specifically developed for the treatment of ophthalmic diseases. The composition of the present invention contains an 0.02% isotonic solution of di- and trisodium salts of echinochrome. The inventors established appropriate conditions under which a chemical interaction between the salt of a weak acid (sodium carbonate) and an organic compound (echinochrome) produces water-soluble sodium derivatives of echinochrome, in which 2 to 3 sodium ions are present per molecule of echinochrome.
Echinochrome, or 2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone, is produced from a natural source (sea urchins, Latin echini), or by chemical synthesis.
The novel pharmaceutical composition Histochrome (trade mark) represents an isotonic solution for injections, containing a mixture of di- and trisodium salts of echinochrome in an amount of 0.018 to 0.022% in an 0.9% sodium chloride solution.
The solution thus prepared is sterilized by filtration through membrane filters and poured into 1 ml ampoules under aseptic conditions in an inert atmosphere. The ready-to-use composition is packaged in batches of 5-10 ampoules into boxes lined with PVC and aluminum foil. The boxes are placed into packs and 10-60 packs are placed into cardboard boxes and labeled in accordance with the requirements. The composition is stored protected from light at a temperature not exceeding 25xc2x0 C. It has a shelf life of 2 years.
The composition is a yellow-brown transparent liquid.
The content of echinochrome, which is formed when Histochrome is acidified with hydrochloric acid, is determined spectrophotometrically. The optical density of a sample of the composition in acidified alcohol is compared with the optical density of a standard solution with a known concentration of echinochrome prepared under identical conditions.
The active ingredient is identified by its spectrum in acidified ethanol, which in the range of 250 to 600 nm has two absorption maxima (342xc2x12 nm and 468xc2x12 nm) and two absorption minima (295xc2x12 nm and 394xc2x12 nm).
The isotonocity of the sample is checked by mercurometric titration of sodium chloride using diphenilcarbazone as an indicator. The content of sodium chloride in the sample is in the range of 0.87% to 0.93%, and the pH is 6.5 to 7.5.
The composition is sterile. Histochrome itself has a marked antimicrobial activity.
The composition of the present invention is effective in the treatment of inflammatory diseases of the cornea, vascular membrane and retina of the eye; in the treatment of trophic disorders and resorption of hemorrhages in the vitreous body and retina. Histochrome may be used in proliferative processes, to reduce edema and to improve epithelization, as well as in the treatment of concussions and penetrating wounds of the eye. The composition has well-pronounced retinoprotective properties, improves characteristics of degenerative processes in the retina and the optic nerve. Histochrome was also found to act as an anticataractic agent.